LC-MS/MS Insight into Vitamin C Restoration to Metabolic Disorder Evoked by Amyloid β in Caenorhabditis elegans CL2006

Abstract

The transitional expression and aggregation of amyloid β (Aβ) are the most important causative factors leading to the deterioration of Alzheimer’s disease (AD), a commonly occurring metabolic disease among older people. Antioxidant agents such as vitamin C (Vc) have shown potential effects against AD and aging. We applied an liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method and differential metabolites strategy to explore the metabolic disorders and Vc restoration in a human Aβ transgenic (Punc-54::Aβ1–42) nematode model CL2006. We combined the LC-MS/MS investigation with the KEGG and HMDB databases and the CFM-ID machine-learning model to identify and qualify the metabolites with important physiological roles. The differential metabolites responding to Aβ activation and Vc treatment were filtered out and submitted to enrichment analysis. The enrichment showed that Aβ mainly caused abnormal biosynthesis and metabolism pathways of phenylalanine, tyrosine and tryptophan biosynthesis, as well as arginine and proline metabolism. Vc reversed the abnormally changed metabolites tryptophan, anthranilate, indole and indole-3-acetaldehyde. Vc restoration affected the tryptophan metabolism and the biosynthesis of phenylalanine, tyrosine and tryptophan. Our findings provide supporting evidence for understanding the metabolic abnormalities in neurodegenerative diseases and the repairing effect of drug interventions.

A bibliometric review on vitamins and Alzheimer’s disease between 1996 and 2023

“…According to the analysis of the co-citation count among the 10 references, most were human experiments, and four were randomized controlled trial (RCTs). The number of citations can be regarded as a relatively reasonable indicator to evaluate the quality of publications, which indicates that vitamins D, E, and B are the focus of current research, but recent research shows that vitamin C supplementation is a feasible strategy for prevention and treatment of AD (Hamid et al, 2022), Vitamin C treatment restored Aβ induced abnormal metabolites, and the role of antioxidants in the repair of AD metabolic disorder provide a new metabonomic observation and explanation (Zhang et al, 2022). Thus, VK2 may also play an important role in the prevention and treatment of AD (Popescu and German, 2021).…”

Cyclocodon lancifolius fruit prolongs the lifespan of Caenorhabditis elegans via antioxidation and regulation of purine metabolism

“…LC-MS/MS analysis was conducted on all supernatants and QC samples, with the analysis parameters being set based on the methods we previously reported. 13…”

“…Synchronization of the worms was achieved using a previously described method. 13 The eggs were moved to NGM plates coated with OP50. After 48 h of incubation, L4 stage worms were collected for subsequent experiments.…”

“…LC-MS/MS analysis was conducted on all supernatants and QC samples, with the analysis parameters being set based on the methods we previously reported. 13 A data processing pipeline resembling the one stated in section 2.3 was employed to conduct the identification of metabolites. Our previous study served as a reference for conducting data analysis and visualization, with minor modifications to the data visualization pipeline.…”

Metabolic Regulations of Smilax china L. against β-Amyloid Toxicity in Caenorhabditis elegans

“…For example, a metabolomic analysis of metabolites from the serum and brain tissue of β-amyloid (Aβ)-induced AD model mice revealed that Bifidobacterium breve treatment can restore Aβ-induced metabolomic disorder related to amino acids [ 22 ]. In our previous study, we used a metabolomic analysis to find that vitamin C can affect the tryptophan metabolism pathway in transgenic C. elegans [ 23 ].…”